Advances in the Application of Antibody Drug Conjugate in Gastric Cancer with Low Expression of Human Epidermal Growth Factor Receptor 2

Abstract

Gastric cancer (GC) is one of the most heterogeneous and aggressive malignant tumors of the digestive system. Traditional chemotherapy drugs and epidermal growth factor receptor 2 (HER2) targeted drugs such as Trastuzumab still have the disadvantages of high incidence of drug resistance, high toxic side effects and poor tolerance of patients. Therefore, it is imperative to develop more effective anti GC drugs. Novel targeted drugs against HER2 are currently available, but are ineffective or resistance in some cases, which is related to the low expression of HER2 (HER2 IHC1+ or IHC2+/ISH-) in certain GC cells, accounting for about 40%-60% of all types. However, in clinical practice, these patients are still reported as HER2-negative GC. Therefore, accurate detection of HER2 expression is crucial to identify patients who may benefit from trastuzumab therapy. The emergence of antibody drug conjugates (ADC) provides a new therapeutic option for HER2-positive GC and it is expected to replace traditional GC chemotherapy in the future by its precise and efficient anti-tumor effect. Recent studies have found that ADC may have potential anti-tumor activity in HER2 low-expression GC, and related clinical studies are evaluating its effectiveness and safety in HER2 low-expression GC treatment. This article reviews the application and the latest research progress of ADC in HER2 low-expression GC patients in the era of targeted therapy and discusses the challenges faced in the application and development of HER2-targeted ADCs.

Keywords

• stomach neoplasms|gastric cancer|human epidermal growth factor receptor 2|low expression of her2 in gastric cancer|antibody drug conjugates|molecular targeted therapy|review